Publications Repository

Publications Repository

View Item 
  •   Home
  • ICR Divisions
  • Other ICR Research
  • View Item
  • Home
  • ICR Divisions
  • Other ICR Research
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

Thumbnail
View/Open
Accepted version (130.1Kb)
Publication Date
2017-03-30
ICR Author
Tutt, Andrew
Author
Ju, YS
Martincorena, I
Gerstung, M
Petljak, M
Alexandrov, LB
Rahbari, R
Wedge, DC
Davies, HR
Ramakrishna, M
Fullam, A
Martin, S
Alder, C
Patel, N
Gamble, S
O'Meara, S
Giri, DD
Sauer, T
Pinder, SE
Purdie, CA
Borg, Å
Stunnenberg, H
van de Vijver, M
Tan, BKT
Caldas, C
Tutt, A
Ueno, NT
van 't Veer, LJ
Martens, JWM
Sotiriou, C
Knappskog, S
Span, PN
Lakhani, SR
Eyfjörd, JE
Børresen-Dale, A-L
Richardson, A
Thompson, AM
Viari, A
Hurles, ME
Nik-Zainal, S
Campbell, PJ
Stratton, MR
Type
Journal Article
Metadata
Show full item record
Abstract
Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
URL
https://repository.icr.ac.uk/handle/internal/705
Collections
  • Other ICR Research
Version of record
10.1038/nature21703
Subject
Adult
Blood Cells
Cell Lineage
Embryo, Mammalian
Embryonic Development
Genome, Human
Germ-Line Mutation
Humans
Mosaicism
Mutagenesis
Mutation
Mutation Rate
Language
eng
Date accepted
2017-02-08
License start date
2017-03-30
Citation
Nature, 2017, 543 (7647), pp. 714 - 718

Browse

All of ICR repositoryICR Divisions & RM Clinical UnitsIssue dateAuthorsTitlesSubjectsThis collectionIssue dateAuthorsTitlesSubjects

Statistics

Most popular itemsStatistics by countryMost popular authors
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.